Abstract
While mRNA vaccines are proving highly efficacious against SARS-CoV-2, it is important to determine how booster doses and prior infection influence the immune defense they elicit, and whether they protect against variants. Focusing on the T cell response, we conducted a longitudinal study of infection-naïve and COVID-19 convalescent donors before vaccination and after their first and second vaccine doses, using a high-parameter CyTOF analysis to phenotype their SARS-CoV-2-specific T cells. Vaccine-elicited spike-specific T cells responded similarly to stimulation by spike epitopes from the ancestral, B.1.1.7 and B.1.351 variant strains, both in terms of cell numbers and phenotypes. In infection-naïve individuals, the second dose boosted the quantity and altered the phenotypic properties of SARS-CoV-2-specific T cells, while in convalescents the second dose changed neither. Spike-specific T cells from convalescent vaccinees differed strikingly from those of infection-naïve vaccinees, with phenotypic features suggesting superior long-term persistence and ability to home to the respiratory tract including the nasopharynx. These results provide reassurance that vaccine-elicited T cells respond robustly to emerging viral variants, confirm that convalescents may not need a second vaccine dose, and suggest that vaccinated convalescents may have more persistent nasopharynx-homing SARS-CoV-2-specific T cells compared to their infection-naïve counterparts.
Highlights
A year and a half since the December 2019 emergence of SARS-CoV-2, the novel betacoronavirus had already infected almost 200 million people and taken the lives of over 4 million, nearly collapsed worldwide health systems, disrupted the global economy, and perturbed society and public health on a scale not experienced within the past 100 years.multiple highly-efficacious vaccines, including the two-dose mRNA-based ones developed by Pfizer/BioNTech and Moderna, which confer ~90% protection against disease, were approved for emergency use before the end of 2020
T cells are important orchestrators and effectors during antiviral immunity. They may hold the key to long-term memory due to their ability to persist for decades, yet these cells have been disproportionately understudied relative to their humoral immune counterparts in the context of COVID-19
We designed a longitudinal study assessing both the frequency and phenotypic characteristics of SARS-CoV-2-specific T cells in order to address the following questions: 1) Do SARS-CoV-2-specific T cells elicited by vaccination respond to ancestral and variant strains?, 2) To what extent is the second dose needed for boosting T cell responses in infection-naïve and convalescent individuals?, and 3) Do vaccine-elicited memory
Summary
A year and a half since the December 2019 emergence of SARS-CoV-2, the novel betacoronavirus had already infected almost 200 million people and taken the lives of over 4 million, nearly collapsed worldwide health systems, disrupted the global economy, and perturbed society and public health on a scale not experienced within the past 100 years.multiple highly-efficacious vaccines, including the two-dose mRNA-based ones developed by Pfizer/BioNTech and Moderna, which confer ~90% protection against disease, were approved for emergency use before the end of 2020. The first variant observed to display a survival advantage was the D614G, which was more transmissible than the original strain and quickly became the dominant variant throughout the world 1. This variant, did not evade immunity and appeared to be more sensitive than the original strain to antibody neutralization by convalescent sera 2. More worrisome was the emergence at the end of 2020 of rapidly-spreading variants in multiple parts of the world, including B.1.1.7, B.1.351, P.1, and B.1.427/B.1.429 (originally identified in United Kingdom, South Africa, Brazil, and California, respectively) 3, followed by additional highly transmissible variants in 2021 including the B.1.617.2 which was first detected in India 4.
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